TGF-β2 interfering oligonucleotides used as adjuvants for microbial vaccines

Abstract

The success of using immune checkpoint inhibitors to treat cancers implies that inhibiting an immunosuppressive cytokine, such as TGF-2, could be a strategy to develop novel adjuvants for microbial vaccines. To develop nucleic acid based TGF-2 inhibitors, we designed three antisense oligonucleotides, designated as TIO1, TIO2, and TIO3, targeting the conserve regions identical in human and mouse TGF-2 mRNA 3 ′-untranslated region. In cultured immune cells, TIO3 and TIO1 significantly reduced the TGF-2 mRNA expression and protein production. In mice, the TIO3 and TIO1, when formulated in various microbial vaccines, significantly enhanced the antibody response to the vaccines, and the TIO3-adjuvanted influenza virus vaccine induced effective protection against the influenza virus challenge. In the immunized mice, TIO3 formulated in microbial vaccines dramatically reduced surface-bound TGF-2 expression on CD4 + T cells and CD19 + B cells in the lymph node (LN) cells and spleen cells; up-regulated the expression of CD40, CD80, CD86, and MHC II molecules on CD19 + B cells and CD11c + dendritic cells; and promoted IFNproduction in CD4 + T cells and CD8 + T cells in the LN cells. Overall, TIO3 or TIO1 could be used as a novel type of adjuvant for facilitating the microbial vaccines to elicit more vigorous and persistent antibody response by interfering with TGF-2 expression.

The trogocytosis of neutrophils on initial transplanted tumor in mice

“… 41 N/A TGF-β2 ASO TIO3 Yao et al., 41 Tu et al. 62 N/A siRNA to Mus musculus Cxcl2 # SIR-93: 5′-CAGUGAACUGCGCUGUCAATT-3′ This paper N/A siRNA to Mus musculus Cxcl2 # SIR-131: 5′-GGGUUGACUUCAAGAACAUTT-3′ This paper N/A siRNA to Mus musculus Cxcl2 # SIR-207: 5′-CACUCUCAAGGGCGGUCAATT-3′ This paper N/A siRNA to Mus musculus Cxcl2 # SIR-Ctrl: 5′-UUCUCCGAACGUGUCACGUTT-3′ This paper N/A Primer to Mus musculus Cxcl2 Forward: 5′-GCGCCCAGACAGAAGTCATA-3′ This paper N/A Primer to Mus musculus Cxcl2 Reverse: 5′-CGAGGCACATCAGGTACGAT-3′ This paper N/A Primer to Mus musculus β-actin Forward: 5′-TGTGACGTTGACATCCGTAA-3′ This paper N/A Primer to Mus musculus β-actin Reverse: 5′-CCACCGATCCACACAGAGTA-3′ This paper N/A Primer to Mus musculus Cxcl10 Forward: 5′-GTCCACGTGTTGAGATCATTGC-3′ This paper N/A Primer to Mus musculus Cxcl10 Reverse: 5′-CTCTGTGTGGTCCATCCTTGG-3′ This paper N/A Primer to Mus musculus Cxcl13 Forward: 5′-ATATGTGTGAATCCTCGTGCCA-3′ This paper N/A Primer to Mus musculus Cxcl13 Reverse: 5′-GGGAGTTGAAGACAGACTTTTGC-3′ This paper N/A Primer to Mus musculus Ccl19 Forward: 5′-CCTTCAGCCTGCTGGTTCTCT-3′ This paper N/A Primer to Mus musculus Ccl19 Reverse: 5′-AGGCTTTCACGATGTTCCCAG-3′ This paper N/A Software and algorithms ImageJ Schneider …”

DNA Oligonucleotides as Antivirals and Vaccine Constituents against SARS Coronaviruses: A Prospective Tool for Immune System Tuning

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The dark side of Tregs during aging

“…Specifically, the use of the IL-10-specific ASOs resulted in a 100-fold increase in anti-OVA antibody titers, associated with an enhanced T cell-mediated specific immune response ( 236 ). Furthermore, TGF-β2-specific ASOs have been formulated for use in various microbial vaccines, which have significantly enhanced the specific antibody response to vaccines ( 237 ).…”